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WO2012123949A8 - Anticorps asymétriques bi- et monospécifiques et leur procédé de génération - Google Patents

Anticorps asymétriques bi- et monospécifiques et leur procédé de génération Download PDF

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Publication number
WO2012123949A8
WO2012123949A8 PCT/IL2012/050093 IL2012050093W WO2012123949A8 WO 2012123949 A8 WO2012123949 A8 WO 2012123949A8 IL 2012050093 W IL2012050093 W IL 2012050093W WO 2012123949 A8 WO2012123949 A8 WO 2012123949A8
Authority
WO
WIPO (PCT)
Prior art keywords
heavy chains
methods
covalent link
generating
identical heavy
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Ceased
Application number
PCT/IL2012/050093
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English (en)
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WO2012123949A1 (fr
Inventor
Itai Benhar
Lilach VAKS
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Ramot at Tel Aviv University Ltd
Original Assignee
Ramot at Tel Aviv University Ltd
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Priority to KR1020137027330A priority Critical patent/KR20140019385A/ko
Priority to CN201280013666.XA priority patent/CN103429619B/zh
Priority to CA2827188A priority patent/CA2827188C/fr
Priority to IN1438MUN2013 priority patent/IN2013MN01438A/en
Priority to AU2012227883A priority patent/AU2012227883A1/en
Priority to EP12716657.7A priority patent/EP2686348B1/fr
Priority to BR112013023653A priority patent/BR112013023653A2/pt
Priority to MX2013010590A priority patent/MX342135B/es
Priority to US14/005,580 priority patent/US9624291B2/en
Priority to JP2013558572A priority patent/JP2014510084A/ja
Application filed by Ramot at Tel Aviv University Ltd filed Critical Ramot at Tel Aviv University Ltd
Publication of WO2012123949A1 publication Critical patent/WO2012123949A1/fr
Publication of WO2012123949A8 publication Critical patent/WO2012123949A8/fr
Priority to IL228442A priority patent/IL228442A/en
Anticipated expiration legal-status Critical
Priority to US15/447,244 priority patent/US10822428B2/en
Ceased legal-status Critical Current

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Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • C07K16/46—Hybrid immunoglobulins
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • C07K16/46—Hybrid immunoglobulins
    • C07K16/468—Immunoglobulins having two or more different antigen binding sites, e.g. multifunctional antibodies
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K39/395—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • C07K16/12—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from bacteria
    • C07K16/1267—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from bacteria from Gram-positive bacteria
    • C07K16/1275—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from bacteria from Gram-positive bacteria from Streptococcus (G)
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
    • C07K16/2878—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against the NGF-receptor/TNF-receptor superfamily, e.g. CD27, CD30, CD40, CD95
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • C07K16/32—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against translation products of oncogenes
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K2039/505—Medicinal preparations containing antigens or antibodies comprising antibodies
    • A61K2039/507—Comprising a combination of two or more separate antibodies
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/30—Immunoglobulins specific features characterized by aspects of specificity or valency
    • C07K2317/31—Immunoglobulins specific features characterized by aspects of specificity or valency multispecific
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
    • C07K2317/52—Constant or Fc region; Isotype
    • C07K2317/522—CH1 domain
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
    • C07K2317/52—Constant or Fc region; Isotype
    • C07K2317/526—CH3 domain
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
    • C07K2317/55—Fab or Fab'
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
    • C07K2317/56—Immunoglobulins specific features characterized by immunoglobulin fragments variable (Fv) region, i.e. VH and/or VL
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/60—Immunoglobulins specific features characterized by non-natural combinations of immunoglobulin fragments

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Immunology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Biochemistry (AREA)
  • Biophysics (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Molecular Biology (AREA)
  • Genetics & Genomics (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Oncology (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Engineering & Computer Science (AREA)
  • Pain & Pain Management (AREA)
  • Rheumatology (AREA)
  • Communicable Diseases (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Microbiology (AREA)
  • Mycology (AREA)
  • Epidemiology (AREA)
  • Peptides Or Proteins (AREA)
  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
  • Micro-Organisms Or Cultivation Processes Thereof (AREA)
  • Preparation Of Compounds By Using Micro-Organisms (AREA)

Abstract

L'invention concerne un anticorps. L'anticorps comprend une région Fc et une région Fab où : (i) la région Fc comprend deux chaînes lourdes non identiques, où au moins une des deux chaînes lourdes non identiques comprend une modification d'acide aminé de façon à former une complémentation entre les deux chaînes lourdes non identiques, augmentant ainsi la probabilité de former des hétérodimères des chaînes lourdes non identiques et diminuant la probabilité de former des homodimères de chaînes lourdes identiques; et (ii) la région Fab comprend une première liaison covalente entre une première chaîne lourde et une première chaîne légère de la région Fab et une seconde liaison covalente entre une seconde chaîne lourde et une seconde chaîne légère de ladite région Fab, où une position de la première liaison covalente par rapport à la première chaîne lourde est différente d'une position de la seconde liaison covalente par rapport à la seconde chaîne lourde. L'invention concerne également des procédés de génération et d'utilisation associés.
PCT/IL2012/050093 2011-03-17 2012-03-15 Anticorps asymétriques bi- et monospécifiques et leur procédé de génération Ceased WO2012123949A1 (fr)

Priority Applications (12)

Application Number Priority Date Filing Date Title
US14/005,580 US9624291B2 (en) 2011-03-17 2012-03-15 Bi- and monospecific, asymmetric antibodies and methods of generating the same
CA2827188A CA2827188C (fr) 2011-03-17 2012-03-15 Anticorps asymetriques bi- et monospecifiques et leur procede de generation
IN1438MUN2013 IN2013MN01438A (fr) 2011-03-17 2012-03-15
AU2012227883A AU2012227883A1 (en) 2011-03-17 2012-03-15 Bi- and monospecific, asymmetric antibodies and methods of generating the same
EP12716657.7A EP2686348B1 (fr) 2011-03-17 2012-03-15 Anticorps asymétriques, bispécifiques et monospécifiques et procédés de génération de ceux-ci
BR112013023653A BR112013023653A2 (pt) 2011-03-17 2012-03-15 anticorpo biespecífico, método de preparação do anticorpo, e composição farmacêutica
MX2013010590A MX342135B (es) 2011-03-17 2012-03-15 Anticuerpos asimetricos, biespecificos y monoespecificos, y metodos para generar los mismos.
KR1020137027330A KR20140019385A (ko) 2011-03-17 2012-03-15 이중특이성 및 단일특이성, 비대칭성 항체 및 이의 제조방법
CN201280013666.XA CN103429619B (zh) 2011-03-17 2012-03-15 双特异性和单特异性、不对称抗体和其制备方法
JP2013558572A JP2014510084A (ja) 2011-03-17 2012-03-15 二重特異性および単一特異性の非対称な抗体ならびにそれらの作製方法
IL228442A IL228442A (en) 2011-03-17 2013-09-15 Specific asymmetric antibodies against me and methods for their preparation
US15/447,244 US10822428B2 (en) 2011-03-17 2017-03-02 Bi-and monospecific, asymmetric antibodies and methods of generating the same

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US201161453591P 2011-03-17 2011-03-17
US61/453,591 2011-03-17

Related Child Applications (2)

Application Number Title Priority Date Filing Date
US14/005,580 A-371-Of-International US9624291B2 (en) 2011-03-17 2012-03-15 Bi- and monospecific, asymmetric antibodies and methods of generating the same
US15/447,244 Continuation US10822428B2 (en) 2011-03-17 2017-03-02 Bi-and monospecific, asymmetric antibodies and methods of generating the same

Publications (2)

Publication Number Publication Date
WO2012123949A1 WO2012123949A1 (fr) 2012-09-20
WO2012123949A8 true WO2012123949A8 (fr) 2013-03-14

Family

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Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/IL2012/050093 Ceased WO2012123949A1 (fr) 2011-03-17 2012-03-15 Anticorps asymétriques bi- et monospécifiques et leur procédé de génération

Country Status (11)

Country Link
US (2) US9624291B2 (fr)
EP (1) EP2686348B1 (fr)
JP (1) JP2014510084A (fr)
KR (1) KR20140019385A (fr)
CN (1) CN103429619B (fr)
AU (1) AU2012227883A1 (fr)
BR (1) BR112013023653A2 (fr)
CA (1) CA2827188C (fr)
IN (1) IN2013MN01438A (fr)
MX (1) MX342135B (fr)
WO (1) WO2012123949A1 (fr)

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BR112013023653A2 (pt) 2016-12-13
CN103429619B (zh) 2017-07-28
KR20140019385A (ko) 2014-02-14
AU2012227883A8 (en) 2013-11-07
AU2012227883A1 (en) 2013-10-24
CA2827188C (fr) 2020-02-11
WO2012123949A1 (fr) 2012-09-20
US20140010814A1 (en) 2014-01-09
MX342135B (es) 2016-09-14
JP2014510084A (ja) 2014-04-24
IN2013MN01438A (fr) 2015-06-12
US9624291B2 (en) 2017-04-18
MX2013010590A (es) 2014-05-27
CA2827188A1 (fr) 2012-09-20
US10822428B2 (en) 2020-11-03
CN103429619A (zh) 2013-12-04
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